Long-Term Safety of Paliperidone Extended Release in Adolescents with Schizophrenia: An Open-Label, Flexible Dose Study.

Abstract

The purpose of this study was to evaluate the long-term safety and tolerability of paliperidone extended-release (ER) in adolescents with schizophrenia. This was a 2 year open-label, multicenter study in adolescents (12-17 years of age, inclusive) with schizophrenia. Eligible patients were initially treated with 6 mg/day paliperidone ER, and the dose could be adjusted between 1.5 and 12 mg/day based on clinical need. Safety parameters were treatment-emergent adverse events (TEAEs), weight, Tanner staging, blood chemistry (including prolactin, glucose, insulin, and lipid levels), and extrapyramidal symptom (EPS) scales. The main efficacy end-point was change from baseline to endpoint in Positive and Negative Syndrome Scale for Schizophrenia (PANSS) total score. Of 400 enrolled patients (mean age, 15.4 years; boys, 61%), 220 were completers. Median (range) exposure was 604.5 (2-765) days. TEAEs were reported in 85.3% of patients; most frequently reported TEAEs included somnolence, increased weight, headache, insomnia, nasopharyngitis, akathisia, schizophrenia exacerbation, and tremor. No deaths were reported. There were no clinically significant mean changes in growth-adjusted z score for change in weight, height, or body mass index (BMI). Tanner ratings showed normal maturation. Most frequently occurring EPS-related events were related to Parkinsonism (15.5%) and hyperkinesia (13.8%). No cases of tardive dyskinesia were reported. Hyperprolactinemia (based on laboratory values) was noted in 56% of patients and 9.3% of patients had prolactin-related TEAEs. A low percentage of patients (4.3%, n=14) had a shift from normal or impaired fasting glucose to high levels. Mean (SD) decrease (improvement) in PANSS total score from baseline to end-point was -19.1 (21.89). The majority of patients had a ≥20% improvement in PANSS total score (responders) from initial treatment with paliperidone ER. Overall, 41.7% of patients achieved remission during the study. Paliperidone ER was generally tolerable, and exhibited efficacy in the maintenance treatment of schizophrenia in adolescents in this large 2 year study.